Cri-du-chat syndrome is an autosome disorder caused by partial deletion (loss) of part of human Chromosome 5 (known as 5p-). This chromosome error occurs during fetal development and is not inherited. The estimated incidence of the syndrome in the United States is 1 in 50,000 live births. Cri-du-chat syndrome affects people of all ethnic backgrounds and is slightly more common in females. It was first described by Jérôme Lejeune in 1963.

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The syndrome gets its name from the characteristic cry of infants born with the disorder. The infant sounds just like a meowing kitten, due to problems with the larynx and nervous system. This cry identifies the syndrome. About 1/3 of children lose the cry by age 2. Other symptoms of cri du chat syndrome may include:

feeding problems because of difficulty swallowing and sucking,

low birth weight and poor growth,

severe cognitive, speech, and motor delays,

behavioral problems such as hyperactivity, aggression, tantrums, and repetitive movements,

Cri du chat syndrome is due to a partial deletion of the short arm of chromosome number 5. Approximately 80% of cases results from a sporadic de novo deletion, while about 10-15% are due to unequal segregation of a parental balanced translocation where the 5p monosomy is often accompanied by a trisomic portion of the genome. The phenotypes in these individuals may be more severe than in those with isolated monosomy of 5p because of this additional trisomic portion of the genome.
Most cases involve terminal deletions with 30-60% loss of 5p material. Fewer than 10% of cases have other rare cytogenetic aberrations (eg, interstitial deletions, mosaicisms, rings and de novo translocations). The deleted chromosome 5 is paternal in origin in about 80% of the cases.

Loss of a small region in band 5p15.2 (cri du chat critical region) correlates with all the clinical features of the syndrome with the exception of the catlike cry, which maps to band 5p15.3 (catlike critical region). The results suggest that 2 noncontiguous critical regions contain genes involved in this condition's etiology. Two genes, Semaphorine F (SEMA5A) and [delta catenin] (CTNND2), which have been mapped to the critical regions are potentially involved in cerebral development and its deletion may be associated in CdCS patients. Also the deletion of the telomerase reverse transcriptase (hTERT) gene localized in 5p15.33 should contribute to the phenotypic changes in CdCS.

Although the size of the deletion varies, a deletion at region 5p15.3 is responsible for the unique cry and deletion at the critical region of 5p15.2 for the other features. The deletion is of paternal origin in about 80% of cases in which the syndrome is de novo.